Effective prevention strategies for HIV are critically needed, and an effective HIV vaccine is the best long-range hope to dramatically reduce the rate of new HIV infections. To this goal, our current understanding of the biology and epidemiology of HIV transmission remains limited. This Program Project will focus on the identification and systematic evaluation of individuals who have been recently infected with HIV and the sexual partners who transmitted HIV to them (Transmission Pairs) to elucidate and quantify epidemiologic, behavioral, biologic, virologic, and host factors that contribute to transmission. The San Diego Primary Infection research group has a long and successful history of recruiting acutely and very recently HIV-infected individuals and their transmitting partners. With new approaches to expand our identification of such study participants, as described in the Clinical and Specimen Core, we will address in Project 1 (Transmission Probability): (Aim 1) the transmission probability per contact ((J), (Aim 2) the rate of partner change (c), (Aim 3) the duration of infectious stages (D), and thus determine the reproductive number (R0) of HIV in this population. These investigations will be complemented with Project 2 (Transmission Correlates) that will identify and quantify the contributions of important biologic (Aim 1), viral (Aim 2), and host (Aim 3) correlates of HIV sexual transmission. Most importantly, this research will allow for the accurate estimation of a potential prevention strategy or candidate vaccine's anticipated efficacy based on both an estimation of the target populations'ongoing risk behavior and a thorough understanding of viral and host factors that contribute to HIV transmission. The Administrative Core (Core A) will play a central role in coordinating the administrative, fiscal, data, and statistical support for this Project as well as providing scientific support and facilitating synergistic interaction among investigators and collaborators critical to the success of the interactive projects. The Clinical and Specimen Core (Core B) will identify, recruit and enroll study subjects and collect, process, store, and manage the clinical specimens needed to meet the objectives of the two proposed research projects.